Abstract 3193: Valosin containing protein (VCP) is a potential novel serum marker for ovarian cancer
Notice bibliographique
Résumé
Abstract The measurement of various serum markers (estradiol, inhibin, MIS) is often performed as an ancillary diagnostic technique for ovarian granulosa cell tumor (GCT), and is widely used for postoperative surveillance for disease recurrence. However, both the sensitivity and specificity of these markers has been repeatedly questioned, and a truly reliable serum marker for GCT has yet to be identified. We have recently developed the Ctnnb1tm1Mmt/+;Ptentm1Hwu/tm1Hwu;Amhr2tm3(cre)Bhr/+ (CPA) transgenic mouse model, which features genetic modifications that mimic pathologically relevant genetic lesions and signaling processes that occur in GCT in women. CPA mice develop anaplastic, highly aggressive GCTs that can spread both by forming distant metastases and by seeding into the peritoneal cavity, which are the main modes of GCT dissemination in women. Due to the biological similarities between GCT in women and in CPA mice, we hypothesized that the CPA model could be used in a translational approach to identify novel serum markers for GCT. To test this, granulosa cells from control mice and GCT cells from CPA mice were placed in culture, and differential secretion or shedding of proteins into the culture supernatant was analyzed by SDSPAGE and silver staining. Proteins bands present in the experimental samples but absent (or present at much lower levels) in control media were isolated from the gels and identified by tryptic digestion followed by LC/MS/MS analyses. By this method, VCL, VCP, HSPA4, HSP90A, HSP70, SPARC, WIF1, CTSB, FAM3C, TIMP2, CFL2 and B2M were found to be selectively secreted/shed by CPA GCT cells. An in vivo validation step was then performed to determined if these proteins were overexpressed in the serum of CPA mice relative to controls. Western blotting showed that CPA mice had elevated (P<0.05) serum levels of VCP, HSP4, CTSB, TIMP2 and B2M. The latter proteins were therefore tested as potential serum diagnostic markers for GCT in a small cohort of women with GCT (n=10) and healthy women (n=7), as well as in patients with ovarian epithelial carcinomas (n=8) to provide an initial assessment of marker specificity. Of the proteins tested, mean serum levels of Valosin Containing Protein (VCP) were found to be over 9-fold higher in women with GCT or ovarian carcinoma relative to healthy women (P<0.01) by western blotting. Furthermore, 90% of women with GCT and 100% of women with ovarian carcinomas had serum VCP levels above the highest level measured in the reference group. While these results indicate that VCP is unlikely to serve as a GCT-specific serum marker, it may nonetheless provide a valuable tool for the diagnosis of ovarian cancer. Analyses of larger cohorts will be required to determine the sensitivity, specificity and predictive values of VCP measurement for various forms and stages of ovarian cancer, as well as to determine if non-ovarian cancers also affect serum VCP levels. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3193. doi:10.1158/1538-7445.AM2011-3193
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».